2-187359330-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005795.6(CALCRL):c.782-58T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.863 in 1,243,314 control chromosomes in the GnomAD database, including 463,646 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.87 (57602 hom., cov: 31)
  • Exomes 𝑓: 0.86 (406044 hom.)
• Consequence: CALCRL NM_005795.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00500

Genes affected

CALCRL (HGNC:16709): (calcitonin receptor like receptor) Enables adrenomedullin binding activity; adrenomedullin receptor activity; and calcitonin gene-related peptide receptor activity. Involved in several processes, including G protein-coupled receptor signaling pathway; cellular response to sucrose stimulus; and receptor internalization. Located in endoplasmic reticulum; endosome; and lysosome. Part of CGRP receptor complex and adrenomedullin receptor complex. Colocalizes with plasma membrane. Implicated in hereditary lymphedema. [provided by Alliance of Genome Resources, Apr 2022]

CALCRL-AS1 (HGNC:55863): (CALCRL and TFPI antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 2-187359330-A-G is Benign according to our data. Variant chr2-187359330-A-G is described in ClinVar as [Benign]. Clinvar id is 1192648.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALCRL	NM_005795.6	c.782-58T>C		intron_variant		ENST00000392370.8
CALCRL-AS1	XR_007087504.1	n.3420-140176A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALCRL	ENST00000392370.8	c.782-58T>C		intron_variant		1	NM_005795.6	P1
CALCRL-AS1	ENST00000412276.6	n.190-140176A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.869 AC: 131928 AN: 151798 Hom.: 57548 Cov.: 31

Gnomad AFR AF: 0.909

Gnomad AMI AF: 0.889

Gnomad AMR AF: 0.818

Gnomad ASJ AF: 0.912

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.802

Gnomad FIN AF: 0.884

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.865

Gnomad OTH AF: 0.870

GnomAD4 exome AF: 0.862 AC: 940807 AN: 1091398 Hom.: 406044 AF XY: 0.860 AC XY: 467543 AN XY: 543446

Gnomad4 AFR exome AF: 0.915

Gnomad4 AMR exome AF: 0.804

Gnomad4 ASJ exome AF: 0.907

Gnomad4 EAS exome AF: 0.756

Gnomad4 SAS exome AF: 0.822

Gnomad4 FIN exome AF: 0.885

Gnomad4 NFE exome AF: 0.866

Gnomad4 OTH exome AF: 0.868

GnomAD4 genome AF: 0.869 AC: 132037 AN: 151916 Hom.: 57602 Cov.: 31 AF XY: 0.867 AC XY: 64405 AN XY: 74260

Gnomad4 AFR AF: 0.909

Gnomad4 AMR AF: 0.818

Gnomad4 ASJ AF: 0.912

Gnomad4 EAS AF: 0.752

Gnomad4 SAS AF: 0.801

Gnomad4 FIN AF: 0.884

Gnomad4 NFE AF: 0.865

Gnomad4 OTH AF: 0.871

Alfa AF: 0.872 Hom.: 9351

Bravo AF: 0.867

Asia WGS AF: 0.794 AC: 2745 AN: 3462

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Lymphatic malformation 8 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	1.5
Dann	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1706287; hg19: chr2-188224057;